Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells

Maria M. Ho, Alvin V. Ng, Stephen Lam, Jaclyn Y. Hung

Research output: Contribution to journalArticle

758 Citations (Scopus)

Abstract

Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the "side population" (SP). In this study, we used flow cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed that SP cells were enriched in tumor-initiating capability compared with non-SP cells. Matrigel invasion assay showed that SP cells also have higher potential for invasiveness. Further characterization of this SP phenotype revealed several stem cell properties. We found evidence for repopulating ability by SP to regenerate a population resembling the original population. SP displayed elevated expression of ABCG2 as well as other ATP-binding cassette transporters and showed resistance to multiple chemotherapeutic drugs. Human telomerase reverse transcriptase expression was higher in the SP, suggesting that this fraction may represent a reservoir with unlimited proliferative potential for generating cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the MCM family of proteins critical to the DNA replication complex, were lower in SP cells, suggesting that a majority of the SP fraction was in the G0 quiescent state. Sixteen clinical lung cancer samples also displayed a smaller but persistent SP population. These findings indicate that SP is an enriched source of lung tumor-initiating cells with stem cell properties and may be an important target for effective therapy and a useful tool to investigate the tumorigenic process.

Original languageEnglish (US)
Pages (from-to)4827-4833
Number of pages7
JournalCancer Research
Volume67
Issue number10
DOIs
StatePublished - May 15 2007

Fingerprint

Neoplastic Stem Cells
Tumor Cell Line
Lung Neoplasms
Side-Population Cells
Population
Stem Cells
Coloring Agents
Minichromosome Maintenance Proteins
Severe Combined Immunodeficiency
ATP-Binding Cassette Transporters
DNA Replication
Heterografts
Neoplasms
Flow Cytometry
Maintenance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. / Ho, Maria M.; Ng, Alvin V.; Lam, Stephen; Hung, Jaclyn Y.

In: Cancer Research, Vol. 67, No. 10, 15.05.2007, p. 4827-4833.

Research output: Contribution to journalArticle

Ho, Maria M. ; Ng, Alvin V. ; Lam, Stephen ; Hung, Jaclyn Y. / Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. In: Cancer Research. 2007 ; Vol. 67, No. 10. pp. 4827-4833.
@article{fd22cd4b16aa4cf197cc8cce847c98c7,
title = "Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells",
abstract = "Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the {"}side population{"} (SP). In this study, we used flow cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed that SP cells were enriched in tumor-initiating capability compared with non-SP cells. Matrigel invasion assay showed that SP cells also have higher potential for invasiveness. Further characterization of this SP phenotype revealed several stem cell properties. We found evidence for repopulating ability by SP to regenerate a population resembling the original population. SP displayed elevated expression of ABCG2 as well as other ATP-binding cassette transporters and showed resistance to multiple chemotherapeutic drugs. Human telomerase reverse transcriptase expression was higher in the SP, suggesting that this fraction may represent a reservoir with unlimited proliferative potential for generating cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the MCM family of proteins critical to the DNA replication complex, were lower in SP cells, suggesting that a majority of the SP fraction was in the G0 quiescent state. Sixteen clinical lung cancer samples also displayed a smaller but persistent SP population. These findings indicate that SP is an enriched source of lung tumor-initiating cells with stem cell properties and may be an important target for effective therapy and a useful tool to investigate the tumorigenic process.",
author = "Ho, {Maria M.} and Ng, {Alvin V.} and Stephen Lam and Hung, {Jaclyn Y.}",
year = "2007",
month = "5",
day = "15",
doi = "10.1158/0008-5472.CAN-06-3557",
language = "English (US)",
volume = "67",
pages = "4827--4833",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells

AU - Ho, Maria M.

AU - Ng, Alvin V.

AU - Lam, Stephen

AU - Hung, Jaclyn Y.

PY - 2007/5/15

Y1 - 2007/5/15

N2 - Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the "side population" (SP). In this study, we used flow cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed that SP cells were enriched in tumor-initiating capability compared with non-SP cells. Matrigel invasion assay showed that SP cells also have higher potential for invasiveness. Further characterization of this SP phenotype revealed several stem cell properties. We found evidence for repopulating ability by SP to regenerate a population resembling the original population. SP displayed elevated expression of ABCG2 as well as other ATP-binding cassette transporters and showed resistance to multiple chemotherapeutic drugs. Human telomerase reverse transcriptase expression was higher in the SP, suggesting that this fraction may represent a reservoir with unlimited proliferative potential for generating cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the MCM family of proteins critical to the DNA replication complex, were lower in SP cells, suggesting that a majority of the SP fraction was in the G0 quiescent state. Sixteen clinical lung cancer samples also displayed a smaller but persistent SP population. These findings indicate that SP is an enriched source of lung tumor-initiating cells with stem cell properties and may be an important target for effective therapy and a useful tool to investigate the tumorigenic process.

AB - Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the "side population" (SP). In this study, we used flow cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed that SP cells were enriched in tumor-initiating capability compared with non-SP cells. Matrigel invasion assay showed that SP cells also have higher potential for invasiveness. Further characterization of this SP phenotype revealed several stem cell properties. We found evidence for repopulating ability by SP to regenerate a population resembling the original population. SP displayed elevated expression of ABCG2 as well as other ATP-binding cassette transporters and showed resistance to multiple chemotherapeutic drugs. Human telomerase reverse transcriptase expression was higher in the SP, suggesting that this fraction may represent a reservoir with unlimited proliferative potential for generating cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the MCM family of proteins critical to the DNA replication complex, were lower in SP cells, suggesting that a majority of the SP fraction was in the G0 quiescent state. Sixteen clinical lung cancer samples also displayed a smaller but persistent SP population. These findings indicate that SP is an enriched source of lung tumor-initiating cells with stem cell properties and may be an important target for effective therapy and a useful tool to investigate the tumorigenic process.

UR - http://www.scopus.com/inward/record.url?scp=34250306257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250306257&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-06-3557

DO - 10.1158/0008-5472.CAN-06-3557

M3 - Article

C2 - 17510412

AN - SCOPUS:34250306257

VL - 67

SP - 4827

EP - 4833

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 10

ER -